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Spontaneous formation of two-dimensional and three-dimensional cholesterol crystals in single hydrated lipid bilayers.

ABSTRACT: Grazing incidence x-ray diffraction measurements were performed on single hydrated bilayers and monolayers of Ceramide/Cholesterol/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocyholine at varying concentrations. There are substantial differences in the phase and structure behavior of the crystalline domains formed within the bilayers relative to the corresponding monolayers, due to interactions between the opposing lipid leaflets. Depending on the lipid composition, these interactions lead to phase separation and formation of cholesterol crystals. The cholesterol and ceramide/cholesterol mixed phases were further characterized at 37°C by immunolabeling with specific antibodies recognizing ordered molecular arrays of cholesterol. Previous studies have shown that cholesterol may nucleate in artificial membranes to form thick two-dimensional bilayer crystals. The study herein demonstrates further growth of cholesterol into three-dimensional crystals. We believe that these results may provide further insight into the formation of cholesterol crystals in early stages of atherosclerosis inflammation.

SUBMITTER: Ziblat R

PROVIDER: S-EPMC3400773 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Spontaneous formation of two-dimensional and three-dimensional cholesterol crystals in single hydrated lipid bilayers.

Ziblat Roy R Fargion Iael I Leiserowitz Leslie L Addadi Lia L

Biophysical journal 20120717 2

Grazing incidence x-ray diffraction measurements were performed on single hydrated bilayers and monolayers of Ceramide/Cholesterol/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocyholine at varying concentrations. There are substantial differences in the phase and structure behavior of the crystalline domains formed within the bilayers relative to the corresponding monolayers, due to interactions between the opposing lipid leaflets. Depending on the lipid composition, these interactions lead to phase ...[more]

PMID: 22853903

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Project description:Cholesterol trafficking, which is an essential function in mammalian cells, is intimately connected to molecular-scale interactions through cholesterol modulation of membrane structure and dynamics and interaction with membrane receptors. Since these effects of cholesterol occur on micro- to millisecond timescales, it is essential to develop accurate coarse-grained simulation models that can reach these timescales. Cholesterol has been shown experimentally to thicken the membrane and increase phospholipid tail order between 0-40% cholesterol, above which these effects plateau or slightly decrease. Here, we showed that the published MARTINI coarse-grained force-field for phospholipid (POPC) and cholesterol fails to capture these effects. Using reference atomistic simulations, we systematically modified POPC and cholesterol bonded parameters in MARTINI to improve its performance. We showed that the corrections to pseudo-bond angles between glycerol and the lipid tails and around the oleoyl double bond particle (the "angle-corrected model") slightly improves the agreement of MARTINI with experimentally measured thermal, elastic, and dynamic properties of POPC membranes. The angle-corrected model improves prediction of the thickening and ordering effects up to 40% cholesterol but overestimates these effects at higher cholesterol concentration. In accordance with prior work that showed the cholesterol rough face methyl groups are important for limiting cholesterol self-association, we revised the coarse-grained representation of these methyl groups to better match cholesterol-cholesterol radial distribution functions from atomistic simulations. In addition, by using a finer-grained representation of the branched cholesterol tail than MARTINI, we improved predictions of lipid tail order and bilayer thickness across a wide range of concentrations. Finally, transferability testing shows that a model incorporating our revised parameters into DOPC outperforms other CG models in a DOPC/cholesterol simulation series, which further argues for its efficacy and generalizability. These results argue for the importance of systematic optimization for coarse-graining biologically important molecules like cholesterol with complicated molecular structure.

Dataset Information

Spontaneous formation of two-dimensional and three-dimensional cholesterol crystals in single hydrated lipid bilayers.

Publications

Spontaneous formation of two-dimensional and three-dimensional cholesterol crystals in single hydrated lipid bilayers.

Similar Datasets

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